Several studies are underway in the RNA Regulation Section to investigate the RBPs and ncRNAs that influence neuronal physiology and pathology, with particular emphasis on neurodegeneration. During this review period, we have studied the role of several RBPs and ncRNAs implicated in Alzheimers disease (AD) as well as other pathologies of the nervous system. We recently reported that the levels of amyloid precursor protein (APP), which is cleaved to release the Alzheimers disease hallmark peptide Abeta, was regulated by RBPs FMRP (fragile X mental retardation protein) and hnRNP C (heterogeneous nuclear ribonucleoprotein C). More recently, we found that the RBP HuD is also linked to Alzheimer's disease (AD) pathogenesis through its interaction with the 3' UTRs of APP mRNA (encoding amyloid precursor protein) and BACE1 mRNA (encoding &#946;-site APP-cleaving enzyme 1), which led to increased half-lives of these mRNAs, and with the long noncoding (lnc)RNA BACE1AS, which partly complements BACE1 mRNA and enhances BACE1 expression. Given that HuD promoted the production of APP and APP-cleaving enzyme, we found that the levels of APP, BACE1, BACE1AS, and A&#946; were higher in the brain of HuD-overexpressing mice. Importantly, cortex (superior temporal gyrus) from patients with AD displayed significantly higher levels of HuD and, accordingly, elevated APP, BACE1, BACE1AS, and A&#946; than did cortical tissue from healthy age-matched individuals. These findings, which appeared in Cell Reports (Kang et al., 2014) led us to propose that HuD jointly promotes the production of APP and the cleavage of its amyloidogenic fragment, Abeta. More recently, we collaborated with Dr. M. Mattsons group towards the discovery that the nontelomeric isoform of telomere repeat-binding factor 2 (TRF2-S) is a novel RBP that regulates axonal plasticity. TRF2-S interacts directly with target mRNAs to facilitate their axonal delivery in a process that is antagonized by fragile X mental retardation protein. Interestingly, FMRP blocks the assembly of TRF2-S-mRNA complexes, and accordingly overexpressing TRF2-S and silencing FMRP promotes mRNA entry to axons, and enhances axonal outgrowth and neurotransmitter release from presynaptic terminals. These findings suggest a function for TRF2-S in an axonal mRNA localization pathway that may regulate local protein synthesis by counteracting FMRP-mediated inhibition, thereby enhancing axonal outgrowth and neurotransmitter release. The work was recently accepted for publication in Nature Communications (Zhang et al., 2015).